Skip to main content
SpringerLink
Log in

Effects of changing hydrogen ion, carbonic acid, and bicarbonate concentrations on bone resorption in vitro

  • Laboratory Investigations
  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Summary

We have examined the effects of H+, CO2, and HCO3 − concentrations during metabolic and respiratory acidosis and alkalosis on bone resorption in vitro. Rat fetal bones prelabeled with45CaCl2 were cultured at 2%, 5%, and 10% CO2 for up to 120 h, and the release of45Ca was measured in devitalized bones (non-cell-mediated45Ca release) and in live bones (cell-mediated45Ca release) cultured with or without PTH and 1,25(OH)2D3. Non-cell-mediated mineral loss was linearly related to H+ concentration but not to CO2 or HCO3 − concentration. This effect was observed on both labeled and stable calcium. Over a wide pH range (6.9–7.5) H+, CO2, or HCO3 − concentrations did not influence cell-mediated bone resorption in control or in PTH-and 1,25(OH)2D3-stimulated cultures. However, inhibition of cell-mediated bone resorption was observed at higher or lower pH irrespective of CO2 or HCO3 − concentrations.

These observations demonstrate that the bone mineral mobilizing effect of acidosis in vitro is mainly due to the effect of changing H+ concentration on devitalized bone. Effects on cell-mediated bone resorption and hormonal response were observed only at extremes of pH. The effects of H+ were independent of changes in CO2 or HCO3 − concentration and could be responsible for the negative calcium balance and increased urinary loss observed in metabolic acidosis in vivo, but do not explain the reported differences in effects on calcium metabolism between respiratory and metabolic acidosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Lemann, J. Jr., Litzow, J.R., Lennon, E.J.: The effects of chronic acid loads in normal man: further evidence for the participation of bone mineral in the defense against chronic metabolic acidosis, J. Clin. Invest.45:1608–1614, 1966

    PubMed  CAS  Google Scholar 

  2. Weber, H.P., Gray, R.W., Dominguez, J.H., Lemann, J. Jr.: The lack of effect of chronic metabolic acidosis on 25-OH-vitamin D metabolism and serum parathyroid hormone in humans, J. Clin. Endocrinol. Metab.43:1047–1055, 1976

    PubMed  CAS  Google Scholar 

  3. Lemann, J. Jr., Litzow, J.R., Lennon, E.J.: Studies of the mechanism by which chronic metabolic acidosis augments urinary calcium excretion in man, J. Clin. Invest.46:1318–1328, 1967

    CAS  PubMed  Google Scholar 

  4. Coe, F.L., Firpo, J.J., Hollandsworth, D.L., Segil, L., Canterbury, J.M., Reiss, E.M.: Effect of acute and chronic metabolic acidosis on serum immunoreactive parathyroid hormone in man, Kidney Int.8:262–273, 1975

    CAS  Google Scholar 

  5. Litzow, J.F., Lemann, J. Jr., Lennon, E.J.: The effect of treatment of acidosis on calcium balance in patients with chronic azotemic renal disease, J. Clin. Invest.46:280–286, 1967

    PubMed  CAS  Google Scholar 

  6. Beck, N., Webster, S.K.: Effects of acute metabolic acidosis on parathyroid hormone action and calcium mobilization, Am. J. Physiol.230:127–131, 1976

    PubMed  CAS  Google Scholar 

  7. Beck, N., Kim, H.P., Kim, K.S.: Effect of metabolic acidosis on renal action of parathyroid hormone, Am. J. Physiol.228:1483–1488, 1975

    PubMed  CAS  Google Scholar 

  8. Martin, K., Freitag, J., Conrades, M., Klahr, S., Slatopolsky, E.: Acidosis enchances the uptake and biological effect of PTH in isolated perfused bone, Clin. Res.26:691, 1978

    Google Scholar 

  9. Raisz, L.G.: Physiological and pharmacological regulation of bone resorption, N. Engl. J. Med.282:909–916, 1970

    Article  PubMed  CAS  Google Scholar 

  10. Sauveur, B., Garabedian, M., Fellot, C., Mongiu, P., Balsan, S.: The effect of induced metabolic acidosis in vitamin D metabolism in rachitic chicks, Calcif. Tissue Res.23:121–124, 1977

    Article  PubMed  CAS  Google Scholar 

  11. Lee, S.W., Russell, J., Avioli, L.V.: 25-Hydroxycholecalciferol to 1,25 dihydroxycholecalciferol: conversion impaired by systemic metabolic acidosis, Science185:994–996, 1977

    Google Scholar 

  12. Gray, S.P., Morris, J.E.W., Brooks, C.J.: Renal handling of calcium magnesium, inorganic phosphate and hydrogen ions during prolonged exposure to elevated carbon dioxide concentrations, Clin. Sci. Mol. Med.45:751–764, 1973

    PubMed  CAS  Google Scholar 

  13. Raisz, L.G., Niemann, I.: Effect of phosphate, calcium and magnesium on bone resorption and hormonal responses in tissue culture, Endocrinology85:446–452, 1969

    PubMed  CAS  Google Scholar 

  14. Raisz, L.G., Holtrop, M.E., Simmons, H.A.: Inhibition of bone resorption by colchicine in organ culture, Endocrinology92:556–562, 1973

    Article  PubMed  CAS  Google Scholar 

  15. Kaye, M., Freuh, A.J., Silverman, M.: A study of vertebral bone powder from patients with chronic renal failure, J. Clin. Invest.49:442–453, 1970

    Article  PubMed  CAS  Google Scholar 

  16. Neuman, W.F., Neuman, M.W.: The Chemical Dynamics of Bone Mineral, pp. 23–38. The University of Chicago Press, Chicago, 1958

    Google Scholar 

  17. Heersche, J.N.M.: The mechanism of osteoclastic bone resorption: a new hypothesis. In J.E. Horton, T.M. Tarpley, and W.F. Davis (eds.): Mechanisms of Localized Bone Loss, Special supplement to Calcified Tissue Abstracts. pp. 437–438. Information Retrieval, Inc., Washington, D.C., 1978

    Google Scholar 

  18. Delling, G., Donath, K.: Morphometrische elektronenmikroskopische and Physikalischemische. Untersuechungen uber die experimentalle osteoporose bei chronischer acidose, Virchows Arch. [Pathol. Anat.]358:321–330, 1973

    Article  CAS  Google Scholar 

  19. Baran, D.T., Lee, S.W., Avioli, L.V.: Acidosis-induced stimulation of 25-hydroxy-D3 1α hydroxylase (1-hydroxylase), 60th Annual Meeting of the Endocrine Society, 1978

  20. Vaes, G.: On the mechanisms of bone resorption the excretion and synthesis of lysosomal enzymes and on the extracellular release of acid by bone cells, J. Cell Biol.39:676–697, 1968

    Article  PubMed  CAS  Google Scholar 

  21. Neuman, W.F., Neuman, M.W.: The Chemical Dynamics of Bone Mineral, pp. 137–168. The University of Chicago Press, Chicago, 1958

    Google Scholar 

  22. Minkin, C., Jennings, J.M.: Carbonic anhydrase and bone remodeling sulfonamide inhibition of bone resorption in organ culture, Science176:1031–1033, 1972

    PubMed  CAS  Google Scholar 

  23. Vaes, G.: Inhibitory actions of calcitonin on resorbing bone explants in culture and on the release of lysosonal enzymes, J. Dent. Res.51:362–366, 1972

    PubMed  CAS  Google Scholar 

  24. Mahgoub, A., Stern, P.H.: Carbon dioxide and the effects of parathyroid hormone on bone in vitro, Am. J. Physiol.226:1272–1275, 1974

    PubMed  CAS  Google Scholar 

  25. Hoffken, B., Parkinson, D.K., Storms, P., Radde, I.C.: Effect of alterations of blood pH on calcium ion activity in rat plasma, Clin. Orthop.78:30–39, 1971

    PubMed  CAS  Google Scholar 

  26. Krukowski, M., Smith, J.J.: pH and the level of calcium in the blood of fetal and neonatal albino rats, Biol. Neonate.29:148–161, 1976

    Article  PubMed  Google Scholar 

  27. Schaefer, K.E.: A concept of the triple tolerance limits based on chronic carbon dioxide toxicity studies, Aerosp. Med.32:197–204, 1961

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, University of Connecticut Health Center, 06032, Farmington, Connecticut, USA

    Jesus H. Dominguez & Lawrence G. Raisz

Authors
  1. Jesus H. Dominguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lawrence G. Raisz
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dominguez, J.H., Raisz, L.G. Effects of changing hydrogen ion, carbonic acid, and bicarbonate concentrations on bone resorption in vitro. Calcif Tissue Int 29, 7–13 (1979). https://doi.org/10.1007/BF02408049

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02408049

Key words

Search

Navigation